Modulation of immune function by the brain via the autonomic nervous system requires that neurotransmitters be released from nerves located near their lymphoid target cells, and that these cells recognize and respond to the signal. We have shown that both noradrenergic nerves and peptidergic nerves innervate lymphoid organs and that nerve terminals come in very close contact with lymphocytes and macrophages in specific lymphoid compartments of these organs, providing a local source of neurotransmitter. Our laboratories and others have shown that lymphoid cells have appropriate noradrenergic and peptidergic receptors, and that these neurotransmitters can influence immune function. This project continuation proposes to define further the specificity of contacts between nerve terminals and lymphoid cells, with an emphasis on peptidergic nerves, using immunocytochemical techniques at the light and ultrastructural levels. In addition, we will investigate the possibility of local cytokine feedback from lymphoid cells to these nerve terminals; such feedback may allow lymphoid cell control over their microenvironment during immune responses. We will use in situ hybridization for IL-1 receptor and IL-2 receptor mRNA in the coeliac-superior mesenteric ganglion (the source of efferent innervation to the spleen) to determine whether these neurons can make appropriate receptors, followed by developing antibody probes for immunocytochemical localization of these receptors on nerve terminals in the spleen. Finally, we will use in oculo culture of splenic fragments to gain a refined understanding about the relationship between nerves and lymphoid cells in a model system that allows control over reinnervation of the transplanted fragment. These three approaches will greatly enhance our understanding of the basic biology of local interactions between nerves and lymphoid cells.